Oluwatomisono I. Akinrimisi1, Pascalle Lucassen1,5, Jean L.J.M. Scheijen2,3, Coco M. Fuhri Snethlage1, Pleun de Groen1, Natal van Riel5, Mark Davids1, Max Nieuwdorp1,4, Casper G. Schalkwijk2,3, Nordin M.J. Hanssen1,4
1Department of Experimental Vascular and Internal Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands; 2CARIM school for cardiovascular disease, Maastricht University, Maastricht, the Netherlands; 3Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; 4Diabeter Center Amsterdam, Amsterdam, Netherlands; 5Department of Computational Biology, Eindhoven University of Technology, Eindhoven, The Netherlands
Methylglyoxal (MGO) is a reactive compound which modifies proteins forming advanced glycation end products and activates inflammatory pathways. Elevated MGO levels have been linked to various diseases. However, its interaction with the gut microbiome remains largely unexplored in clinical settings.
To investigate this relationship data from 457 individuals with type 1 diabetes from the GUTDM1 cohort were used (63.89% female; median age: 40 years (IQR: 28–53); median BMI: 24.68 kg/m² (IQR: 22.59–27.44). This study analyzed fecal metagenomics, plasma metabolomics, alongside paired fecal and plasma MGO targeted (ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)) measurements.
Plasma and fecal MGO levels were negatively correlated with time in range (Spearman ρ = -0.22, p<0.01) and (Spearman ρ = -0.14, p<0.01), respectively. A weak positive correlation was observed between plasma and fecal MGO (Spearman ρ = 0.10, p<0.05). Using urinary c-peptide creatinine ratio (UCPCR) as a marker for residual beta cell function, higher plasma MGO levels were observed in the low/undetectable group compared to the intermediate/high group (p<0.01). No significant differences were observed for fecal MGO between the UCPCR groups. Fecal MGO levels were predicted from the gut microbiome composition using an XGBoost model, with predictions having a correlation of (Spearman ρ = 0.26, p<0.05) with actual values. The genera Ruminococcus, Actinomyces, Collinsella, Eubacteriales unclassified, and Candidatus Cibionibacter contributed most to the model performance. Microbial pathways showed modest associations to fecal MGO, but plasma MGO was neither predictable from microbiome data nor significantly correlated with pathways.
Our findings suggest that MGO is associated with poor glycemic control and reduced beta cell function. They also suggest that plasma and fecal MGO are influenced by distinct physiological processes, with specific microbes linked to MGO levels.
This research was supported by an NWO VIDI grant